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      Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering

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          Abstract

          Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR.

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          Most cited references28

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          Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds.

          Tissue engineering is a new and exciting technique which has the potential to create tissues and organs de novo. It involves the in vitro seeding and attachment of human cells onto a scaffold. These cells then proliferate, migrate and differentiate into the specific tissue while secreting the extracellular matrix components required to create the tissue. It is evident, therefore, that the choice of scaffold is crucial to enable the cells to behave in the required manner to produce tissues and organs of the desired shape and size. Current scaffolds, made by conventional scaffold fabrication techniques, are generally foams of synthetic polymers. The cells do not necessarily recognise such surfaces, and most importantly cells cannot migrate more than 500 microm from the surface. The lack of oxygen and nutrient supply governs this depth. Solid freeform fabrication (SFF) uses layer-manufacturing strategies to create physical objects directly from computer-generated models. It can improve current scaffold design by controlling scaffold parameters such as pore size, porosity and pore distribution, as well as incorporating an artificial vascular system, thereby increasing the mass transport of oxygen and nutrients into the interior of the scaffold and supporting cellular growth in that region. Several SFF systems have produced tissue engineering scaffolds with this concept in mind which will be the main focus of this review. We are developing scaffolds from collagen and with an internal vascular architecture using SFF. Collagen has major advantages as it provides a favourable surface for cellular attachment. The vascular system allows for the supply of nutrients and oxygen throughout the scaffold. The future of tissue engineering scaffolds is intertwined with SFF technologies.
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            Bone tissue engineering: a review in bone biomimetics and drug delivery strategies.

            Critical-sized defects in bone, whether induced by primary tumor resection, trauma, or selective surgery have in many cases presented insurmountable challenges to the current gold standard treatment for bone repair. The primary purpose of a tissue-engineered scaffold is to use engineering principles to incite and promote the natural healing process of bone which does not occur in critical-sized defects. A synthetic bone scaffold must be biocompatible, biodegradable to allow native tissue integration, and mimic the multidimensional hierarchical structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold is capable of eluting bioactive molecules (e.g., BMPs, TGF-betas, etc., to accelerate extracellular matrix production and tissue integration) or drugs (e.g., antibiotics, cisplatin, etc., to prevent undesired biological response such as sepsis or cancer recurrence) in a temporally and spatially controlled manner. Various biomaterials including ceramics, metals, polymers, and composites have been investigated for their potential as bone scaffold materials. However, due to their tunable physiochemical properties, biocompatibility, and controllable biodegradability, polymers have emerged as the principal material in bone tissue engineering. This article briefly reviews the physiological and anatomical characteristics of native bone, describes key technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an overview of local drug delivery as it pertains to bone tissue engineering is included. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.
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              Controlled growth factor delivery for tissue engineering.

              Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2014
                23 July 2014
                : 2014
                : 940860
                Affiliations
                1Laboratory of Immune Regulation and Tissue Engineering, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
                2Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, USA
                3Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA
                4Department of Periodontology, Graduate School of Medicine, Ewha Womans University, Seoul, Republic of Korea
                5Dental Research Center (DRC) and Tissue Engineering Unit (TERU), Qassim College of Dentistry, Qassim University, Saudi Arabia
                6Laboratory of Immune Regulation and Tissue Engineering (LITE), Division of Periodontology, Diagnostic Sciences & Dental Hygiene, Ostrow School of Dentistry, University of Southern California, 925 34th Street, Room 4278, Los Angeles, CA 90089-0641, USA
                Author notes
                *Homayoun H. Zadeh: zadeh@ 123456usc.edu

                Academic Editor: Seong-Hun Kim

                Author information
                http://orcid.org/0000-0001-7965-0927
                Article
                10.1155/2014/940860
                4132312
                25147826
                0a11d0f4-1083-46d0-a15f-b62b2526dff5
                Copyright © 2014 Sahar Ansari et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 May 2014
                : 2 July 2014
                Categories
                Research Article

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